Biology subjects

Da Silva, E.

Publications and source records attributed to Da Silva, E..

3 recordsLinked to original sources

bioRxiv2026

Encoding neuronal shape in the stochastic dynamics of branching processes

Cell shape critically influences function, yet how complex and reproducible morphologies emerge from stochastic cellular dynamics remains unclear. Here, we investigate dendritic morphogenesis of two classes of Drosophila mechanosensory neurons with contrasting architectures, combining in vivo live imaging, quantitative analysis, cytoskeletal perturbations, and computational modeling. We show that despite sharing similar local stochastic branching rules, the two classes exhibit divergent growth dynamics that cannot be explained by standard, diffusive growth models. This discrepancy arises because Class I neurons display subdiffusive branch dynamics over long timescales, unlike Class IV. Based on these findings, we develop a minimal model with only four parameters that separates short-and long-term branch behaviors, and successfully recapitulates growth dynamics and final morphologies in both classes. Cytoskeletal perturbations reveal a functional separation between actin, which drives short-term exploratory branch fluctuations and arbor expansion, and microtubules, which tune long-term branch diffusivity and determine class-specific morphology. Together, these results establish a parsimonious, generalizable framework linking local cytoskeletal regulation to global neuronal architecture and reveal how stochastic dynamics encode reproducible cell shapes.

biophysics↗

bioRxiv2025

Spatial patterning of contractility by a mechanogen gradient underlies Drosophila gastrulation

During development cell deformations are spatially organized, however, how cellular mechanics is spatially controlled is unclear. Spatial control of cell identity often determines local cellular mechanics in a two-tiered mechanism (1). Theoretical studies also proposed that molecular gradients, so called "mechanogens", spatially control mechanics (2, 3). We report evidence of such a "mechanogen" required for Drosophila gastrulation. We show that the GPCR ligand Fog, expressed in the posterior endoderm (4-6), diffuses and acts in a concentration-dependent manner to activate actomyosin contractility at a distance during a wave of tissue invagination. While Fog is uniformly distributed in the extracellular space, it forms a surface-bound gradient that activates Myosin-II via receptor oligomerization. This activity gradient self-renews as the wave propagates and is shaped by both receptor endocytosis and a feedback mechanism involving adhesion to the vitelline membrane by integrins. This exemplifies how chemical, mechanical and geometrical cues underly the emergence of a self-organized mechanogen activity gradient.

developmental biology↗

bioRxiv2017

ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup

The most commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. Little is known about the cells-of-origin for non-functional neuroendocrine tumors. Here, we genotyped 64 PanNETs for mutations in ATRX, DAXX, and MEN1 and found 37 tumors (58%) carry mutations in these three genes (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis on 33 randomly selected cases to reveal two distinct subgroups with one group consisting entirely of A-D-M mutant PanNETs. Two biomarkers differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX gene expression and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha cells (pval < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells.

cancer biology↗